Skip to main content

Advertisement

SpringerLink
Log in

Genetic loci influencing kidney function and chronic kidney disease

  • Brief Communication
  • Published:

From Nature Genetics

View current issue Submit your manuscript

Abstract

Using genome-wide association, we identify common variants at 2p12–p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10−10 to 10−15). Of these, rs10206899 (near NAT8, 2p12–p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 × 10−5 and P = 3.6 × 10−4, respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1: Architecture of the loci associated with creatinine in the genome-wide association study.

Similar content being viewed by others

References

  1. Levey, A.S. et al. Kidney Int. 72, 247–259 (2007).

    Article  CAS  Google Scholar 

  2. Köttgen, A. et al. Nat. Genet. 41, 712–717 (2009).

    Article  Google Scholar 

  3. Kopp, J.B. et al. Nat. Genet. 40, 1175–1184 (2008).

    Article  CAS  Google Scholar 

  4. Stevens, L.A., Coresh, J., Greene, T. & Levey, A.S. N. Engl. J. Med. 354, 2473–2483 (2006).

    Article  CAS  Google Scholar 

  5. Price, A.L. et al. Nat. Genet. 38, 904–909 (2006).

    Article  CAS  Google Scholar 

  6. Dyda, F., Klein, D.C. & Hickman, A.B. Annu. Rev. Biophys. Biomol. Struct. 29, 81–103 (2000).

    Article  CAS  Google Scholar 

  7. Kharasch, E.D. Clin. Pharmacol. Ther. 84, 158–162 (2008).

    Article  CAS  Google Scholar 

  8. Lash, L.H., Fisher, J.W., Lipscomb, J.C. & Parker, J.C. Environ. Health Perspect. 108 Suppl 2, 177–200 (2000).

    Article  CAS  Google Scholar 

  9. Marshall, J.D., Beck, S., Maffei, P. & Naggert, J.K. Eur. J. Hum. Genet. 15, 1193–1202 (2007).

    Article  CAS  Google Scholar 

  10. Mattoo, A. & Goldfarb, D.S. Semin. Nephrol. 28, 181–191 (2008).

    Article  CAS  Google Scholar 

  11. Ciccia, A. et al. Mol. Cell 25, 331–343 (2007).

    Article  CAS  Google Scholar 

  12. Fujita, T., Urban, T.J., Leabman, M.K., Fujita, K. & Giacomini, K.M. J. Pharm. Sci. 95, 25–36 (2006).

    Article  CAS  Google Scholar 

  13. Filipski, K.K., Mathijssen, R.H., Mikkelsen, T.S., Schinkel, A.H. & Sparreboom, A. Clin. Pharmacol. Ther. 86, 396–402 (2009).

    Article  CAS  Google Scholar 

  14. Naiche, L.A., Harrelson, Z., Kelly, R.G. & Papaioannou, V.E. Annu. Rev. Genet. 39, 219–239 (2005).

    Article  CAS  Google Scholar 

  15. Chapman, D.L. et al. Dev. Dyn. 206, 379–390 (1996).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Study-specific acknowledgments are provided in the Supplementary Note. We thank S. Asquith and J. Collier at K-bioscience for their help with the replication genotyping.

Author information

Author notes

  1. John C Chambers, Weihua Zhang, Liz Lightstone, James Scott, Gerjan Navis, Paul Elliott and Jaspal S Kooner: These authors contributed equally to the work.

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College of London, London, UK

    John C Chambers, Weihua Zhang, Marjo-Riitta Jarvelin & Paul Elliott

  2. Ealing Hospital National Health Service (NHS) Trust, Middlesex, UK

    John C Chambers, Weihua Zhang, Joban S Sehmi, Ranil de Silva & Jaspal S Kooner

  3. Department of Nephrology and Transplantation, King's College London, UK

    Graham M Lord, Maria Hernandez-Fuentes & Esperanza Perucha

  4. Medical Research Council (MRC) Centre for Transplantation, King's College London, UK

    Graham M Lord, Maria Hernandez-Fuentes & Esperanza Perucha

  5. National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre, Guy's and St. Thomas' NHS Foundation Trust and King's College London, London, UK

    Graham M Lord, Maria Hernandez-Fuentes & Esperanza Perucha

  6. University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Pim van der Harst, Stephan J L Bakker, Henk J G Bilo & Gerjan Navis

  7. MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK

    Debbie A Lawlor & George Davey Smith

  8. National Heart and Lung Institute, Hammersmith Hospital Campus, Imperial College London, London, UK

    Joban S Sehmi, Ranil de Silva, James Scott & Jaspal S Kooner

  9. Division of Medicine, University College London, London, UK

    Daniel P Gale & Patrick H Maxwell

  10. Structural Bioinformatics Group, Imperial College London, London, UK

    Mark N Wass & Michael J E Sternberg

  11. Twin Research and Genetic Epidemiology Department, King's College London, St. Thomas' Hospital Campus, London, UK

    Kourosh R Ahmadi, Ioana Cotlarciuc, Nicole Soranzo & Timothy D Spector

  12. Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland

    Jacqui Beckmann

  13. University Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

    Murielle Bochud

  14. Clinical Pharmacology Unit, University of Cambridge, Addenbrookes Hospital, Cambridge, UK

    Morris J Brown

  15. Clinical Pharmacology and The Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK

    Mark J Caulfield & Patricia B Munroe

  16. Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK

    John M C Connell & Anna Dominiczak

  17. Department of Histopathology, Imperial College, Hammersmith Hospital, London, UK

    H Terence Cook

  18. Department of Gastroenterology and Hepatology, Imperial College London, London, UK

    Guohong Deng

  19. Division of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium

    Olivier Devuyst & Céline Maréchal

  20. Isala Clinics, Zwolle, The Netherlands

    Lambert D Dikkeschei

  21. Center for Renal Diseases, Zvezdara University Medical Center, Belgrade, Serbia

    Nada Dimkovic

  22. South West Thames Institute for Renal Research, Epsom and St. Helier University Hospitals NHS Trust, Carshalton, UK

    Mark Dockrell & Marta Lapsley

  23. London School of Hygiene and Tropical Medicine, London, UK

    Shah Ebrahim

  24. Department of Human Genetics, Rheinisch-Westfaelische Technische Hochschule University Hospital Aachen, Aachen, Germany

    Thomas Eggermann & Klaus Zerres

  25. Cardiovascular Medicine, University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford, UK

    Martin Farrall

  26. National Institute of Aging, Clinical Research Branch–Longitudinal Studies Section, Baltimore, Maryland, USA

    Luigi Ferrucci & Toshiko Tanaka

  27. Department of Nephrology and Clinical Immunology, RWTH University Hospital Aachen, Aachen, Germany

    Jurgen Floege & Georg Schlieper

  28. MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK

    Nita G Forouhi, Ruth J F Loos, Jian'an Luan & Nicholas J Wareham

  29. Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Ron T Gansevoort & Marc A J Seelen

  30. Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA

    Xijin Han, Yun Li & Goncalo R Abecasis

  31. Department of Clinical Sciences, Lund University, Malmö, Sweden

    Bo Hedblad, Olle Melander & Marketa Sjögren

  32. Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands

    Jaap J Homan van der Heide

  33. Department of Transplantation Immunology, University Medical Center Groningen, Groningen, The Netherlands

    Bouke G Hepkema

  34. Centre of Epidemiology for Child Health, University College London Institute of Child Health, London, UK

    Elina Hypponen

  35. Department of Medical Genetics, University of Lausanne and the Swiss Institute of Bioinformatics, Lausanne, Switzerland

    Toby Johnson

  36. Langerhans Medical Research Group, Zwolle, The Netherlands

    Paul E de Jong & Nanne Kleefstra

  37. Department of Epidemiology, Unit of Genetic Epidemiology and Bioinformatics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Vasiliki Lagou & Harold Snieder

  38. Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

    Karin Luttropp & Louise Nordfors

  39. Division of Nephrology, University of Maryland School of Medicine, Baltimore, Maryland, USA

    Afshin Parsa

  40. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

    Leena Peltonen

  41. Institute for Molecular Medicine Finland (FIMM), Nordic European Molecular Biology Laboratory (EMBL) Partnership for Molecular Medicine, Biomedicum Helsinki 2U and University of Helsinki, Helsinki, Finland

    Leena Peltonen

  42. National Institute for Health and Welfare, Helsinki, Finland

    Leena Peltonen, Anneli Pouta & Marjo-Riitta Jarvelin

  43. Department of Psychiatry, Institute for Research in Extramural Medicine (EMGO), Neuroscience Campus, Vrije Universiteit (VU) Medical Center, Amsterdam, The Netherlands

    Brenda W Penninx & Johannes H Smit

  44. Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands

    Brenda W Penninx & Johannes H Smit

  45. Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Brenda W Penninx & Johannes H Smit

  46. Institute of Health Sciences, University of Oulu, Oulu, Finland

    Anneli Pouta & Marjo-Riitta Jarvelin

  47. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    Inga Prokopenko & Mark I McCarthy

  48. Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK

    Inga Prokopenko & Mark I McCarthy

  49. Oxford NIHR Biomedical Research Centre, Oxford, UK

    Inga Prokopenko & Mark I McCarthy

  50. University of Southampton, Southampton, UK

    Paul J Roderick

  51. Department of Clinical Chemistry, Institute of Clinical Medicine, University of Oulu, Oulu, Finland

    Aimo Ruokonen

  52. Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK

    Nilesh J Samani

  53. Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Cagliari, Italy

    Serena Sanna & Manuela Uda

  54. Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

    Martin Schalling

  55. Laboratory of Genetics, US National Institutes of Health Biomedical Research Center, National Institute on Aging, Baltimore, Maryland, USA

    David Schlessinger

  56. Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA

    Alan R Shuldiner

  57. Division of Renal Medicine K56, Karolinska University Hospital at Huddinge, Stockholm, Sweden

    Peter Stenvinkel

  58. Chemical Pathology, Guy's and St Thomas' Hospitals Trust, London, UK

    Ramasamyiyer Swaminathan

  59. General Practice 't Veen, Hattem, The Netherlands

    Lielith J Ubink-Veltmaat

  60. Department of Internal Medicine, University Hospital Center, University of Lausanne, Lausanne, Switzerland

    Peter Vollenweider & Gerard Waeber

  61. Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge, UK

    Chris Wallace

  62. Medical Genetics, Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, King of Prussia, Pennsylvania, USA

    Dawn Waterworth & Vincent Mooser

  63. Biocenter Oulu, University of Oulu, Oulu, Finland

    Marjo-Riitta Jarvelin

  64. Division of Medicine, Renal Section, Hammersmith Hospital Campus, Imperial College London, London, UK

    Liz Lightstone

  65. Department of Epidemiology and Public Health, MRC-HPA Centre for Environment and Health, Imperial College of London, London, UK

    Paul Elliott

Authors
  1. John C Chambers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weihua Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Graham M Lord
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pim van der Harst
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Debbie A Lawlor
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joban S Sehmi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Daniel P Gale
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mark N Wass
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kourosh R Ahmadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Stephan J L Bakker
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jacqui Beckmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Henk J G Bilo
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Murielle Bochud
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Morris J Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Mark J Caulfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. John M C Connell
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. H Terence Cook
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Ioana Cotlarciuc
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. George Davey Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Ranil de Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Guohong Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Olivier Devuyst
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Lambert D Dikkeschei
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Nada Dimkovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Mark Dockrell
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Anna Dominiczak
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Shah Ebrahim
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Thomas Eggermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Martin Farrall
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Luigi Ferrucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. Jurgen Floege
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. Nita G Forouhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  33. Ron T Gansevoort
    View author publications

    You can also search for this author in PubMed Google Scholar

  34. Xijin Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  35. Bo Hedblad
    View author publications

    You can also search for this author in PubMed Google Scholar

  36. Jaap J Homan van der Heide
    View author publications

    You can also search for this author in PubMed Google Scholar

  37. Bouke G Hepkema
    View author publications

    You can also search for this author in PubMed Google Scholar

  38. Maria Hernandez-Fuentes
    View author publications

    You can also search for this author in PubMed Google Scholar

  39. Elina Hypponen
    View author publications

    You can also search for this author in PubMed Google Scholar

  40. Toby Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  41. Paul E de Jong
    View author publications

    You can also search for this author in PubMed Google Scholar

  42. Nanne Kleefstra
    View author publications

    You can also search for this author in PubMed Google Scholar

  43. Vasiliki Lagou
    View author publications

    You can also search for this author in PubMed Google Scholar

  44. Marta Lapsley
    View author publications

    You can also search for this author in PubMed Google Scholar

  45. Yun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  46. Ruth J F Loos
    View author publications

    You can also search for this author in PubMed Google Scholar

  47. Jian'an Luan
    View author publications

    You can also search for this author in PubMed Google Scholar

  48. Karin Luttropp
    View author publications

    You can also search for this author in PubMed Google Scholar

  49. Céline Maréchal
    View author publications

    You can also search for this author in PubMed Google Scholar

  50. Olle Melander
    View author publications

    You can also search for this author in PubMed Google Scholar

  51. Patricia B Munroe
    View author publications

    You can also search for this author in PubMed Google Scholar

  52. Louise Nordfors
    View author publications

    You can also search for this author in PubMed Google Scholar

  53. Afshin Parsa
    View author publications

    You can also search for this author in PubMed Google Scholar

  54. Leena Peltonen
    View author publications

    You can also search for this author in PubMed Google Scholar

  55. Brenda W Penninx
    View author publications

    You can also search for this author in PubMed Google Scholar

  56. Esperanza Perucha
    View author publications

    You can also search for this author in PubMed Google Scholar

  57. Anneli Pouta
    View author publications

    You can also search for this author in PubMed Google Scholar

  58. Inga Prokopenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  59. Paul J Roderick
    View author publications

    You can also search for this author in PubMed Google Scholar

  60. Aimo Ruokonen
    View author publications

    You can also search for this author in PubMed Google Scholar

  61. Nilesh J Samani
    View author publications

    You can also search for this author in PubMed Google Scholar

  62. Serena Sanna
    View author publications

    You can also search for this author in PubMed Google Scholar

  63. Martin Schalling
    View author publications

    You can also search for this author in PubMed Google Scholar

  64. David Schlessinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  65. Georg Schlieper
    View author publications

    You can also search for this author in PubMed Google Scholar

  66. Marc A J Seelen
    View author publications

    You can also search for this author in PubMed Google Scholar

  67. Alan R Shuldiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  68. Marketa Sjögren
    View author publications

    You can also search for this author in PubMed Google Scholar

  69. Johannes H Smit
    View author publications

    You can also search for this author in PubMed Google Scholar

  70. Harold Snieder
    View author publications

    You can also search for this author in PubMed Google Scholar

  71. Nicole Soranzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  72. Timothy D Spector
    View author publications

    You can also search for this author in PubMed Google Scholar

  73. Peter Stenvinkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  74. Michael J E Sternberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  75. Ramasamyiyer Swaminathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  76. Toshiko Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  77. Lielith J Ubink-Veltmaat
    View author publications

    You can also search for this author in PubMed Google Scholar

  78. Manuela Uda
    View author publications

    You can also search for this author in PubMed Google Scholar

  79. Peter Vollenweider
    View author publications

    You can also search for this author in PubMed Google Scholar

  80. Chris Wallace
    View author publications

    You can also search for this author in PubMed Google Scholar

  81. Dawn Waterworth
    View author publications

    You can also search for this author in PubMed Google Scholar

  82. Klaus Zerres
    View author publications

    You can also search for this author in PubMed Google Scholar

  83. Gerard Waeber
    View author publications

    You can also search for this author in PubMed Google Scholar

  84. Nicholas J Wareham
    View author publications

    You can also search for this author in PubMed Google Scholar

  85. Patrick H Maxwell
    View author publications

    You can also search for this author in PubMed Google Scholar

  86. Mark I McCarthy
    View author publications

    You can also search for this author in PubMed Google Scholar

  87. Marjo-Riitta Jarvelin
    View author publications

    You can also search for this author in PubMed Google Scholar

  88. Vincent Mooser
    View author publications

    You can also search for this author in PubMed Google Scholar

  89. Goncalo R Abecasis
    View author publications

    You can also search for this author in PubMed Google Scholar

  90. Liz Lightstone
    View author publications

    You can also search for this author in PubMed Google Scholar

  91. James Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

  92. Gerjan Navis
    View author publications

    You can also search for this author in PubMed Google Scholar

  93. Paul Elliott
    View author publications

    You can also search for this author in PubMed Google Scholar

  94. Jaspal S Kooner
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

J.C.C., P.E., L.L., J.S., G.N. and J.S.K. designed the study. J.C.C., W.Z., D.A.L. and P.v.d.H. led the data analysis. J.C.C., P.E., L.L., J.S., G.N. and J.S.K. wrote the manuscript, with contributions from all the authors.

Corresponding authors

Correspondence to John C Chambers or Jaspal S Kooner.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Methods, Supplementary Note, Supplementary Tables 1–6 and Supplementary Figures 1–6 (PDF 798 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chambers, J., Zhang, W., Lord, G. et al. Genetic loci influencing kidney function and chronic kidney disease. Nat Genet 42, 373–375 (2010). https://doi.org/10.1038/ng.566

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.566

  • Springer Nature America, Inc.

This article is cited by

Search

Navigation